Clofarabine plus Low-Dose Cytarabine for the Treatment of Patients with Higher-Risk Myelodysplastic Syndrome (MDS) who have been Relapsing after, or are Refractory to, Hypomethylator Therapy
The goal of this clinical research study is to learn if clofarabine when given in combination with cytarabine can help to control myelodysplastic syndrome (MDS) after the disease could not be controlled with standard therapy. The safety of this treatment will also be studied. Clofarabine is designed to interfere with the growth and development of cancer cells. Cytarabine is designed to insert itself into DNA (the genetic material of cells) of cancer cells and stop the DNA from repairing itself.
Disease Group: Leukemia
Treatment Agent: Clofarabine
Treatment Location: Only at MDACC
Primary objectives The primary objective is to assess complete response (CR) rate and overall survival Secondary objectives The secondary objectives are to assess duration of response, relapse-free survival, and the safety profile
IRB Review and Approval Date: 11/16/2011
Recruitment Status: Not Accepting
Projected Accrual: N/A
1) Age >/= 18 years.
2) Diagnosis of MDS confirmed within 10 weeks prior to study entry according to WHO or FAB criteria. Patients are either not eligible for or choose not to proceed with a stem cell transplant.
3) MDS classified as follows: RAEB-1 (5%-9% BM blasts); RAEB-2 (10%-19% BM Blasts); CMML (5%-19% BM blasts); RAEB-t (20%-29% BM blasts) AND/OR by IPSS: intermediate-2 and high risk patients.
4) No response, progression, or relapse (according to 2006 IWG criteria; see section 8 for details) following at least 4 cycles of either azactidine or decitabine, or following at least 2 cycles of SGI-110, which were completed within the last 2 years - AND/OR - intolerance to azacitidine, decitabine, or SGI-110 defined as drug-related >/= grade 3 hepatic or renal toxicity leading to treatment discontinuation during the preceding 2 years.
5) Eastern Cooperative Oncology Group (ECOG) performance status of </= 2.
6) Willing to adhere to and comply with all prohibitions and restrictions specified in the protocol.
7) Patient (or patient's legally authorized representative) must have signed an informed consent document indicating that the patient understands the purpose of and proecdures required for the study and is willing to participate in the study.
1) Uncontrolled intercurrent illness including, but not limited to,
symptomatic congestive heart failure, unstable angina pectoris, or
2) Active infection not adequately responding to appropriate antibiotics (i.e. ongoing temperatures of >/= 38 degree Celsius).
3) Total bilirubin >/= 1.5 mg/dL and not related to hemolysis or Gilbert's disease. Patients with total bilirubin >/= 1.5 mg/dL to 3 mg/dL are eligible if at least 75% of the bilirubin is indirect.
4) Alanine transaminase (ALT/SGPT) or aspartate transaminase (AST/SGOT) >/= 2.5 x the upper limit of normal.
5) Serum creatinine > 1.5 mg/dL.
6) Female patients who are pregnant or lactating.
7) Patients with reproductive potential who are unwilling to following contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine devices [IUD], double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization) throughout the study.
8) Female patients with reproductive potential who do not have a negative urine or blood beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening.
9) Patients receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy.
10) No prior treatment with cytarabine or clofarabine. Prior hydroxyurea for control of leukocytosis or use of hematopoietic growth factors (eg, G-CSF, GM-CSF, procrit, aranesp, thrombopoietins) is allowed at any time prior to or during study if considered to be in the best interest of the patient.
11) Psychiatric illness or social situation that would limit the patient's ability to comply with study requirements.